SYNTHESIS, ABSOLUTE-CONFIGURATION AND PHARMACOLOGICAL EVALUATION OF TIAPROFENIC ACID ANTIPODES

Dextrorotatory and levorotatory antipodes (RU 40518, RU 40519) of the non-steroidal antiinflammatory drug (NSAID) racemic tiaprofenic acid ( RU 15060) have been prepared by means of a new patented stereoconversi on process. Unlike other arylpropionic acids, their absolute configura tions, determined by circular dichroism, were R for the dextrorotatory enantiomer and S for the levorotatory enantiomer. Pharmacological eva luation showed that R-(+)-RU 40518 displays a potent in vitro inhibiti on of guinea-pig polymorphonuclear leukocytes (PMNL) cyclooxygenase an d in vivo a better analgesic activity than its racemate or S-(-)-RU 40 519 on the writhing test in the rat. Racemate and enantiomers showed s imilar antiinflammatory activity in carrageenan-induced paw oedema in the rat. These findings indicate that unlike other NSAIDs, the dextror otatory enantiomer R is the active antipode for tiaprofenic acid.